Rats fed diets which contain relatively high levels (20%) unsaturated fat are much more likely to develop mammary adenocarcinoma after exposure to either 7,12-dimethylbenz(a) anthracene (DMBA) or N-nitrosomethylurea (NMU), compared to rats fed low fat (2%) diets. In addition, rats fed high fat diets develop tumors after a shorter latent period, their tumors grow more rapidly, and they develop more tumors per tumor-bearing rat when compared to rats fed low fat diets. High fat diets also enhance tumor transplantability. In some cases, inhibitors of prostagladin synthesis, prevent the tumor growth-promoting effect of the high unsaturated fat diets. In other cases, the growth of both induced and transplanted tumors is inhibited by indomethacin and/or aspirin which inhibit the cyclooxygenase pathway. The serum concentration of linoleic acid, which is the major unsaturated fatty acid in corn oil, increases about 3-fold in rats fed diets containing 20% corn oil compared to rats fed diets containing 2% linoleic acid. Linoleic acid is converted by a number of different tissues to arachidonic acid, which is further metabolized via the lipoxygenase or cyclooxygenase pathways. Products of the cyclooxygenase pathway include prostaglandins (E1,E2,I2,F1Alpha,F2Alpha) and thromboxanes. It is clear that at least some products provided via the cyclooxygenase pathway (PGE1 and PGE2) regulate immune responses. Other evidence suggests that the growth of carcinogen-induced mammary tumors is influenced by immune responses and that these responses are inhibited, particularly in rats which are fed high fat diets. Hence, a series of experiments are proposed to determine (a) if the protective effects of indomethacin (or other inhibitors of the cyclooxygenase pathway) are limited by the quantity of unsaturated fat in the diet, (b) if tumor growth in lymph nodes and other metastatic sites is inhibited by indomethacin, (c) if serum levels of fatty acids (precursors for prostaglandins) and/or the production of prostaglandins may be influenced by the quantity of dietary fat, (d) if indomethacin alters either serum levels of fatty acids or the production of prostaglandins, and (e) if prostaglandins or other products of the cyclooxygenase pathway affect the growth of cultured mammary tumor cells and how these products affect immunogolical functions of lymphoid cells.